EMD-45185

Single-particle
2.53 Å
EMD-45185 Deposition: 04/06/2024
Map released: 21/08/2024
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-45185

Cutibacterium acnes 50S ribosomal subunit with Clindamycin bound

EMD-45185

Single-particle
2.53 Å
EMD-45185 Deposition: 04/06/2024
Map released: 21/08/2024
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Cutibacterium acnes
Sample: 50S subunit with Clindamycin bound
Fitted models: 9c4g

Deposition Authors: Lomakin IB , Devarkar SC, Bunick CG
Mechanistic Basis for the Translation Inhibition of Cutibacterium acnes by Clindamycin.
Lomakin IB , Devarkar SC, Grada A , Bunick CG
(2024) J Invest Dermatol. , 144 , 2553 - 2561.e3
PUBMED: 39122144
DOI: doi:10.1016/j.jid.2024.07.013
ISSN: 1523-1747
Abstract:
Inflammation and the Gram-positive anaerobic bacterium Cutibacterium acnes, which is implicated in acne pathogenesis and pilosebaceous-unit inflammation, are the main targets of antibiotic-based therapy against acne vulgaris (acne). The most widely used antibiotics in acne therapy are tetracyclines, macrolides, and lincosamides. Unfortunately, C. acnes bacteria over the past several decades have demonstrated increased resistance to these antibiotics, particularly to clindamycin. The precise knowledge of how antibiotics interact with their clinical target is needed to overcome this problem. Toward this goal, we determined the structure of clindamycin in complex with the ribosome of C. acnes at 2.53 Å resolution using cryogenic electron microscopy. The galactose sugar moiety of clindamycin interacts with nucleotides of the 23S ribosomal RNA directly or through a conserved network of water-mediated interactions. Its propyl pyrrolidinyl group interacts with the 23S ribosomal RNA through van der Waals forces. Clindamycin binding to the C. acnes ribosome interferes with both: proper orientation of the aminoacyl group of the A-site bound transfer RNA that is needed for peptide bond formation and with the extension of the nascent peptide. Our data are important for advancing the understanding of antibiotic resistance and development of narrow-spectrum antibacterial drugs, which is an urgent need for contemporary antibiotic stewardship.